The DOI matches its Crossref record; 50 of the 50 references it cites were found in a registry or an index.
B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells
Open accessAbstract
B cells have paradoxical roles in autoimmunity, exerting both pathogenic and protective effects. Pathogenesis may be antibody independent, as B cell depletion therapy (BCDT) leads to amelioration of disease irrespective of autoantibody ablation. However, the mechanisms of pathogenesis are poorly understood. We demonstrate that BCDT alleviates central nervous system autoimmunity through ablation of IL-6–secreting pathogenic B cells. B cells from mice with experimental autoimmune encephalomyelitis (EAE) secreted elevated levels of IL-6 compared with B cells from naive controls, and mice with a B cell–specific IL-6 deficiency showed less severe disease than mice with wild-type B cells. Moreover, BCDT ameliorated EAE only in mice with IL-6–sufficient B cells. This mechanism of pathogenesis may also operate in multiple sclerosis (MS) because B cells from MS patients produced more IL-6 than B cells from healthy controls, and this abnormality was normalized with B cell reconstitution after Rituximab treatment. This suggests that BCDT improved disease progression, at least partly, by eliminating IL-6–producing B cells in MS patients. Taking these data together, we conclude that IL-6 secretion is a major mechanism of B cell–driven pathogenesis in T cell–mediated autoimmune disease such as EAE and MS.
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B-cell depletion with rituximab in relapsing-remitting multiple sclerosis
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Self-citationToll Pathway-Dependent Blockade of CD4 + CD25 + T Cell-Mediated Suppression by Dendritic Cells
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B cells regulate autoimmunity by provision of IL-10
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IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis
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BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells
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Cited by
IL-6 as a keystone cytokine in health and disease
Hunter, C. A., & Jones, S. A. (2015) · Nature Immunology · doi:10.1038/ni.3153 · Cited by 2,511
Immunopathology of multiple sclerosis
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Self-citationB cell depletion therapies in autoimmune disease: advances and mechanistic insights
Lee, D. S. W., Rojas, O. L., & Gommerman, J. L. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-00092-2 · Cited by 658
Metadata
- Authors
- Barr, T. A., Shen, P., Brown, S., Lampropoulou, V., Roch, T., Lawrie, S., Fan, B., O’Connor, R. A., Anderton, S. M., Bar-Or, A., Fillatreau, S., & Gray, D.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2012-04-30
- Volume
- 209
- Issue
- 5
- Pages
- 1001-1010
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2154132418
- Cited by
- 649
- References
- 50
- FWCI
- 36.79
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Barr, T. A., Shen, P., Brown, S., Lampropoulou, V., Roch, T., Lawrie, S., Fan, B., O’Connor, R. A., Anderton, S. M., Bar-Or, A., Fillatreau, S., & Gray, D. (2012). B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20111675
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